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Preliminary information
Anatomy and physiology '''Neurons''' are electrically-excitable cells that conduct signals through themselves via the movement of electrically-charged atoms (ions) through them and into the neighbouring areas. For an introduction for the lay people (it is actually written for kids so it is rather well-explained) may be found [https://faculty.washington.edu/chudler/ap.html here]). '''Synapses''' are junctions between two neurons, at which the head of one and the tail of the other meet to send signals (usually either chemical or electrical) between each other. A single neuron can have dozens of different synapses with other neurons. The pathways of dopamine, basically a path of interconnected neurons (via synapses) that signal to each other via, amongst other neurotransmitters, dopamine. The '''brain areas''' are '''explained''', in lay terms, in [http://serendip.brynmawr.edu/bb/kinser/Structure1.html this] page. The '''mesolimbic pathway''' connects two parts of the brain: the '''ventral tegmental area''' (VTA) and the '''nucleus accumbens''' (NAc) and is believed to be involved in pleasure, mood, emotions, ''etc.'' It is also believed to be overactive in schizophrenia and this is believed to be responsible for the so called “positive symptoms” of the disorder, such as hallucinations and delusions. There is also the '''mesocortical pathway''' which connects the VTA with the frontal cortex. This pathway is believed to be involved in cognition, specifically the following aspects: working memory, attention, decision-making, problem-solving, impulse control, ''etc.'' It is believed to be underactive in people with attention-deficit hyperactivity disorder and schizophrenia. Sometimes the '''mesolimbic and mesocortical circuits''' may be considered one and called the '''mesocorticolimbic pathway'''. The last one in the human brain is called the '''nigrostriatal pathway''', which connects the substantia nigra and striatum and controls our voluntary movements, it is the pathway that is gradually destroyed in '''Parkinson’s disease'''. '''Autonomous nervous system''' (ANS), is a division of the nervous system that controls our various involuntary movements like those of our heart muscle, our diaphragm (which compresses our chest when we breathe), our digestive tract, our glands (these secrete hormones, saliva, sweat, tears, stomach acid, ''etc.''), ''etc.'' '''Gastrointestinal (GI) tract''', the digestive tract. '''Hepatic''', liver. '''Renal''', kidney. '''Genitourinary tract''', the kidneys, bladder and sex organs. '''Sympathetic nervous system''' (SNS), is a subdivision of the ANS that, along with the parasympathetic branch of the ANS (PNS) works to control our various involuntary movements. The SNS has basically the opposite actions on our involuntary movements as the PNS and is responsible for controlling breathing rate, the width of the airways (most drugs for asthma act on the SNS) and heart rate. The SNS is often called the “fight or flight” response, its actions in the ANS is usually on the more immediate functions of the ANS, like heart rate, breathing rate, ''etc.'' '''Parasympathetic nervous system''' (PNS) is a subdivision of the ANS that is often called the “rest and digest” division, its actions are on housekeeping functions like controlling the secretions of glands, the movement of the various components of the digestive tract (hence PNS inhibitors are known to cause constipation), ''etc.'' Its chief neurotransmitter is acetylcholine. '''White blood cell''' (WBC), the cells of the immune system that defend our bodies from infections and cancer. The prefix “leuco”, “leuko” or “leuk” usually refers to WBCs. For example leukaemia is a cancer of the WBCs, likewise leucopenia (also spelt leukopenia by Americans) is an abnormally low number of WBCs in the blood. '''Central nervous system''' (CNS), the brain and spinal cord. '''Peripheral nervous system''' (PNS), parts of the nervous system that are outside the CNS. '''Blood-brain barrier''' (BBB), the barrier of cells that separates the blood in the periphery from the blood in the CNS. Reuptake, is basically the process by which neurotransmitters get taken up by the so called “reuptake pumps” which terminate their activity in the synapse. Consequently, reuptake inhibitors prolong the activity of the neurotransmitter in question. '''Neuromuscular junction''' – synapses that connect muscle cells to the nervous system. They relay signals from the nerves to the muscles, such as the signal to contract or relax a muscle. '''Electrocardiogram''' (ECG, also known as an EKG) – a method of measuring the electrical activity of the heart. See the heart is the only organ that has its own, self-contained nervous system, beside the brain of course. This nervous system controls its rhythm. ECGs are usually written on a piece of paper by the machine being used to give such readings, usually these readings have several identifiable parts, which can be measured in size (i.e., their duration). One component is the QT interval, which, if prolonged, can lead to fatal cardiac arrest. Vasculature – blood vessels, such as arteries and veins. '''Cardiovascular''', the veins and arteries supplying blood to and taking blood away from the heart. '''Cerebrovascular''', the veins and arteries supply blood to and taking blood away from the brain. '''Nervous system''' – a collection of neurons that communicate with each other via synapses and form a functional, potentially independent (such as in the case of the brain or heart’s nervous system) of all external inputs. Pharmacology and chemistry '''Neurotransmitters''', basically compounds that serve as chemical messengers between neurons. '''Physical dependence''' – a state in which one’s body has become so used to a particular substance that it sort of assumes that the substance is always going to be there, consequently, whenever a dependent individual stops taking said substance they will develop a constellation of symptoms known as the withdrawal syndrome. '''Physical dependence''' does not imply addiction, although addiction does imply some degree of physical dependence. See '''addiction''' requires two additional features: drug-seeking behaviour and craving for the drug must be part of the withdrawal syndrome. Physical dependence can occur with a few different non-addictive medications such as antipsychotics, antidepressants and β-blockers (blood pressure medicines). This is because if somebody on these medications abruptly stops these medications it will usually cause them to experience withdrawal symptoms. '''Addiction''' is believed to be a form of '''maladaptive memory''', which seems to involve a multitude of different neurotransmitters and brain functions and involve irreversible changes in brain structure and function. Amongst the various factors that appear to influence risk of addiction genetics, environment, ''etc.'' One of the major neurotransmitters that appear to be implicated is glutamate, which is involved in neuroplasticity. Which is the ability of synaptic connections to strengthen or weaken over time. '''Enzyme''', a large molecule (usually either a protein or made from nucleic acids) that catalyses (speeds up) a biochemical reaction, even though it not modified in any way by the biochemical reaction it catalyses. '''Substrates''' are substances prior to the biochemical reaction that enzymes accelerate. '''Enzymes catalyse''' chemical reactions by binding to the substrate in a manner that favours the chemical reaction they catalyse over no reaction. '''Enzyme inhibition''' – basically the process by which the activity of an enzyme is reduced, it can be: '''competitive''', '''non-competitive''', '''epigenetic''' and '''uncompetitive'''. '''Competitive inhibitors''' inhibit the enzyme’s activity by competing for the enzyme’s active site, which is where it catalyses the various biochemical reactions it acts on. '''Uncompetitive inhibitors''' are substances that only bind to the enzyme when it is in the process of catalysing a biochemical process and this binding is not the active site, but rather a different site that reduces the catalytic efficiency of the enzyme. '''Non-competitive inhibitors''' are a lot like the uncompetitive inhibitors, but unlike them they have no preference for the enzyme while it is catalysing the biochemical reaction or prior to when it is bound by the substrate. '''Catabolism''' and '''anabolism''' – catabolism is the breakdown of a substance into simpler molecules; anabolism is the adding on to a substance. '''Amino acids''' (link: [[Wikipedia:Amino_acids|G]]), the building blocks of proteins. There are 21 amino acids found in proteins. Refer to the figure below for their structures. '''Cell''', the base unit of life. Cells have several different components, including their cell wall that gives the cell structure and separates what is outside the cell from what is inside the cell, their mitochondria (energy production-centre) and nucleus (sort of like the brain of the cell which contains its genetic code. '''Gene expression''', basically the process by which genetic code gets converted into proteins in the nucleus of a cell. This, in turn, gives the cell the various properties that their genetic code them. See figure 3 for details of the structure for animal cells. '''Catecholamine neurotransmitters''' is a class of neurotransmitters (chemical messengers between brain, spinal cord and nerve cells) that are derived from L-DOPA metabolism in the body. They include: adrenaline, noradrenaline and dopamine. See the figure below for the biosynthesis of pathway of the catecholamines. '''Dopamine''' (DA) is a catecholamine neurotransmitter that our bodies synthesize from L-tyrosine (an amino acid), after first turning it into L-DOPA (levodopa; this is also a drug to treat Parkinson’s; brand names: Duodopa, Kinson, Sinemet). Most addictive drugs increase dopamine levels in the MLP indirectly, that is, they do not bind to any receptor or other protein that directly regulates dopamine release in the MLP, but rather work via a sophisticated network of receptors and brain cells, that in turn, leads to said increase in dopamine in the MLP. Roles for other neurotransmitters in drug dependence also exists, including: serotonin, noradrenaline, GABA and glutamate. Although stimulants violate this general rule and do in fact bind to receptors and other proteins that directly regulate dopamine release in the MLP. Monoamine neurotransmitters, neurotransmitters with one amine group (see the figure below) attached to a ring or rings. '''Serotonin''' (5-hydroxytryptamine, abbreviated 5-HT (which is used for receptors)) is a monoamine neurotransmitter, with other roles in the body, which is biosynthesized from the amino acid L-tryptophan. Its roles are diverse and include: in sleep, memory, learning, perception, mood, addiction, blood clotting, stomach acid secretion, temperature regulation, digestive tract motility (how food moves through the digestive tract) and appetite. '''Melatonin''' is a hormone and neurotransmitter that is involved in mostly regulating sleep. Although a role in mood has also been suggested, based on the efficacy of a melatonin agonist and 5-HT2C antagonist, [[wikipedia:agomelatine|agomelatine]]. See the figure below for the structures of melatonin, serotonin and their precursors. '''Histamine''', a chemical signalling molecule that has diverse roles in the CNS and the periphery. It is biosynthesized from the amino acid histidine. In the CNS it acts via the H1 and H3 receptors, which are both metabotropic receptors, H1 is excitatory while H3 is an inhibitory auto- and hetero- receptor. H1 receptor activation improves wakefulness, whereas blocking this receptor is responsible for the sedating effect of many drugs, especially the first antihistamines to be developed. In the periphery it acts via H1, H2 and H4 receptors all of which are metabotropic receptors. H1 receptors play a crucial role in mediating allergic responses in the body, it is via blocking this receptor that the family of drugs, the antihistamines, achieve their anti-allergy effects. H2 receptors, on the other hand, is secreted by the cells of the stomach in order to induce the release of stomach acid. Consequently H2 antagonists produce inhibitory effects on the release of stomach acid and are used to treat stomach ulcers and related conditions. H4 receptors are expressed primarily in immune cells and appears to play a role in immune responses, similarly to the H1 receptor. '''Glutamate''', '''aspartate''', '''γ-aminobutyric acid''' (GABA), '''glycine''', '''D-alanine''' and '''D-serine''' are '''amino acid neurotransmitters''' that act, primarily, at ionotropic receptors. Glycine, serine, alanine, aspartate and glutamate all activate the NMDA ionotropic glutamate receptor and the binding of both glutamate/aspartate and serine/alanine/glycine (where / means “or”) at their respective sites on the receptor is required for the receptor to be activated. AMPA and kainate receptors are also glutamate receptors and are also ionotropic receptors. Glutamate also has a number of metabotropic receptors named the metabotropic glutamate receptors and numbered 1-8 (given the abbreviation mGluR1-8). They generally act by either inhibiting or potentiating the activity of nearby ionotropic receptors, or regulating the release of glutamate. Glutamate’s ionotropic receptors are all excitatory, that is, they increase the electrical excitability of the neurons on which they are expressed. Glycine also has its own ionotropic receptor called the glycine receptors which are inhibitory and are found primarily in the spinal cord. GABA binds to two major receptor types – GABAA and GABAB receptors, both of which are inhibitory in nature, GABAA is an ionotropic receptor whereas GABAB is a metabotropic receptor. '''Acetylcholine''', a neurotransmitter that is involved in various functions in the body, it is the chief neurotransmitter at the neuromuscular junction and plays a crucial role in cognition, movement control, perception, mood and various other neurological functions. It is biosynthesized from choline, an essential B group vitamin. See below for their structures. It binds to two distinct families of receptor – the '''nicotinic acetylcholine receptors''' (nAChRs), which are excitatory ionotropic receptors found primarily in the CNS, adrenal medulla and neuromuscular junction and the '''muscarinic acetylcholine receptors''' (mAChRs) which are metabotropic receptors found primarily in the PNS and CNS. nAChRs comes in various subunits, which are expressed in different tissues of the body. '''Anandamide''' (AEA) and '''2-arachidonoylglycerol''' (2-AG), are two '''endocannabinoids''', that is, substances that are produced by the body on demand to activate the two cannabinoid receptors (both of which are metabotropic), CB1 and CB2. CB1 is found primarily in the CNS, but also in the testes. CB2 is found primarily in the immune system. '''Monoamine oxidase''' (MAO) – two enzymes, MAO-A and MAO-B, which catalyse the breakdown of the monoamine neurotransmitters. MAO-A preferentially breaks down serotonin, melatonin, adrenaline and noradrenaline, whereas MAO-B preferentially breaks down the trace amines, phenethylamine and benzylamine. Both degrade dopamine equally, as well as tyramine (which is a trace amine and sympathomimetic amine that is also found in certain foods like fermented foods like aged cheeses, certain alcoholic beverages, vegemite, marmite, ''etc.''), although they are both expressed (i.e., found in appreciable quantities) in different tissues. MAO-A is preferentially expressed in the liver and digestive tract, whereas MAO-B is preferentially expressed in the brain, although MAO-A is also found in the CNS. Tyramine build-up is responsible for a fairly common reaction seen in those people that are on non-subtype-selective monoamine oxidase inhibitors (MAOIs) like phenelzine and tranylcypromine, both of which are used to treat depression (albeit rarely) when they eat tyramine-laced foods, which can be fatal if enough tyramine is ingested (usually via a hypertensive crisis). Both subtypes are expressed in the brain and liver, but only MAO-A is expressed in the intestinal wall, which means that MAO-A is responsible for much of the degradation of dietary tyramine before it makes its way to the liver for further metabolism (which occurs to all drugs/compounds that enter our bodies).Shulman, KI; Herrmann, N; Walker, SE (October 2013). "Current place of monoamine oxidase inhibitors in the treatment of depression.". ''CNS Drugs'' '''27''' (10): 789–97. [http://dx.doi.org/10.1007/s40263-013-0097-3 doi:10.1007/s40263-013-0097-3]. PMID 23934742. '''Enantiomer''', a particular mirror form of a molecule, either dextrorotatory (abbreviated as “dextro” or “dex”) or levorotatory (“levo” or “lev”). For example see the two enantiomers of amfetamine (the figure below). '''Dosage form''', the delivery system of a drug, whether it be a tablet, capsule, nasal spray, needle, ''etc.'' '''Enzyme''', usually a protein that speeds up chemical reactions, which normally are usually pretty slow when unaided. '''Receptor''', usually a protein that changes biological processes, they can be bound by drugs or poisons, which can activate, block (preventing other substances from activating said receptor) or inversely activate (basically activate a receptor in a way that causes the opposite effect to the endogenous ligand). Examples of receptors include the '''monoamine receptors''', such as the '''serotonin receptors''' (which are numbered 5-HT1-7, with a few subtypes belonging to the 5-HT1 and 5-HT2 families being alphabetized from A to F for family 1 and A to C for family 2), '''adrenergic receptors''' (that respond to adrenaline and noradrenaline; two subgroups – α1-2 (also subdivided into alphabetized subtypes) and β1-3), '''dopamine receptors''' (D1-5) and '''trace amine-associated receptors''' (only ones that exist in humans are TAAR1,2,5,6,8,9). There are '''two major types of receptor''' – '''ionotropic''' (or ligand-gated ion channels) and '''metabotropic'''. Ionotropic receptors mediate rapid signalling and produce near instant changes in cellular function, whereas metabotropic receptors produce comparatively slow changes in cellular function (they are slow on a cellular level, but they are near instant, relative to how fast we can process information, to us humans, usually), their signalling methods are usually significantly more sophisticated and usually includes their ability to increase/reduce the production of second messengers like cyclic adenosine monophosphate (cAMP) or cyclic guanine monophosphate (cGMP). They often also have functions on ion channels, hence affecting electrical excitability. Ionotropic receptors only exist in electrically-excitable cells as only electrically-excitable cells are susceptible to the changes in electrical excitability produced by ionotropic receptor activation. Ionotropic receptors often have significant effects on neurotransmitter release in the synaptic cleft of several neurons. Most monoamine receptors are metabotropic, with the following sole exception: 5-HT3 receptors. There are also '''autoreceptors''' which reduce the release of the neurotransmitter that they respond to, and '''heteroreceptors''' that reduce the release of a different neurotransmitter than the one that they respond to. '''Endogenous''', body-synthesized and hence naturally occurring in the body. For instance, endogenous monoamines are monoamines that the body naturally synthesizes, most often from amino acids. Endogenous ligand, body-synthesized compounds that the body uses to naturally activate specific receptors. '''Agonist''', a substance that activates a receptor. '''Antagonist''', a substance that blocks a receptor, preventing agonists from binding to the receptor, in order to activate said receptor. '''Partial agonists''', serve as agonists that produce a less complete activation of the receptor in question, when compared to full agonists. '''Full agonists''' produce an activation of the receptor, in question, that is equivalent to that produced by the endogenous ligand. Inverse agonists, elicit the reverse biologic response of agonists (hence why they are called “inverse” agonists). Many drugs we initially thought were antagonists were in fact inverse agonists like antihistamines, for example. The entire process of '''absorption''', '''distribution''' through the tissues of the body, '''metabolism''' and '''excretion''' is called, collectively, the '''pharmacokinetics''' of a drug. '''Bioavailability''', the percentage of a particular drug that makes it from the dosage form into circulation in the blood. Metabolism, the process by which the body converts a drug or poison into something the body is better equipped at disposing of, most often due to the superior water-solubility of said by-product (which is called a metabolite), when compared to the drug/poison. See a substance must be water soluble in order for the body to excrete it in the urine. Excretion, the process by which the body removes a drug and/or its metabolites from the body. Most often in urine and faeces. '''Elimination''', the combined process of metabolism and excretion. '''Elimination half-life''', the amount of time the body requires in order to eliminate half of the quantity of drug originally in the body. Drug regulation '''Food and Drug Administration''' (FDA) is a division of the U.S. Government’s Department of Health and Human Services, that decides which drugs and foods are allowed to be used by the general public. '''Therapeutic Goods Administration''' (TGA) is a division of the ''Australian Government’s'' '''Department of Health and Ageing''' that decides which medicines can be marketed in Australia. '''European Medicines Agency''' (EMA), an agency of the '''European Union''' (EU) that decides which medicines can be marketed in the EU. '''Medicines and Healthcare Products Regulatory Agency''' (MHRA), a division of the Her Majesty’s Government that dictates which drugs can be sold in the '''United Kingdom'''. Australia '''The Standard for the Uniform Scheduling of Medicines and Poisons''' (SUSMP) is a document that despite the fact it does not actually hold any legal standing in Australia (as the different states have their own drug laws, but this is usually based heavily on the SUSMP), it usually gives one pretty accurate guides as to the legal status of the availability/distribution of drugs (such as which drugs can be advertised on TV, in magazines, ''etc.'') and as to who can and who cannot sell/prescribe drugs. The latest version may be found here. The SUSMP includes eight distinct schedules, numbered 2 to 9. '''Schedule 1''' is intentionally left blank. '''Schedule 2''' are pharmacy medicines, that is, drugs that can only be sold in a pharmacies (although personal permits are sometimes given out), although they can be sold by any adult (over the age of 16) employees of these pharmacies without a pharmacist taking any part in the transaction. There is no need for a prescription for these medicines. '''Schedule 3''' consists of pharmacist-only medicines, which are medicines that can be dispensed by a pharmacist only, that is, a pharmacist must have some role in the transaction. '''Schedule 4''' consists of prescription-only medicines for either humans or animals. '''Schedules 5-7''' are poisons that become increasingly restricted as the schedule number goes up. '''Schedule 8''' consists of controlled drugs that are illegal to possess without authority (like a prescription or due to one supplying the drug for therapeutic use [like a nurse giving the drug to a patient in hospital or a pharmacist dispensing the drug at a pharmacy]), but are perfectly legal for medical use. There are also tighter controls on the distribution and use so as to prevent misuse. '''Schedule 9''' consists of prohibited drugs that are illegal to possess except for select research purposes. The appendices of SUSMP as are follows: United Kingdom In the United Kingdom drugs are regulated under the ''Misuse of Drugs Act. 1971'' as either class A, class B or class C drugs.Joint Formulary Committee (2013). ''British National Formulary (BNF)'' (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85-711084-8. pp. 8. '''Class A''' drugs are ones that are most prone to abuse and have the harshest penalties for possession without authority (like a prescription). They include: diamorphine (heroin) and other intravenous opioids (like pethidine, morphine, dipipanone, etc.), cocaine, lysergide (LSD), methadone, MDMA (ectasy), phencyclidine and class B substances when injected. '''Class B''' drugs are amfetamines, barbiturates, cannabis, codeine, ethylmorphine, glutethimide, nabilone, pentazocine, phenmetrazine and pholcodine, which are drugs that can be abused and have a significant potential for abuse, but are less prone to abuse than class A drugs. '''Class C''' drugs are drugs with minimal potential for abuse, like chlorphentermine, benzfetamine, buprenorphine, amfepramone, mazindol, meprobamate, pemoline, pipradol, most benzodiazepines, zolpidem, androgenic and anabolic steroids and other hormones with abuse potential. Another act, the ''Misuse of Drugs Regulations 2001'', divides drugs up into 5 schedules, in an analogous way to how they are divided in Australia and the U.S. '''Schedule 1''' consists of drugs that are not used medically, like lysergide, and are prohibited to possess, except with special authority from the Home Office. '''Schedule 2''' consists of drugs that are used medically but are of very high abuse potential like class A drugs. '''Schedule 3''' consists of drugs that are used medically and of a lower, but not low, potential for abuse than schedule 2 drugs. Examples are barbiturates (except secobarbital), buprenorphine, amfepramone, midazolam, pentazocine, phentermine and temazepam. '''Schedule 4''' consists of drugs found in class C. '''Schedule 5''' drugs are drugs that includes preparations of such strength, but low potential for abuse that they are subject to minimal control, aside from the requirement that any prescriptions and invoices are kept for 2 years. United States In the United States drugs are divided into five distinct schedules, each assigned '''Roman numerals I to V'''.[http://www.fda.gov/regulatoryinformation/legislation/ucm148726.htm "Controlled Substances Act"]. ''FDA.gov''. Silver Spring, USA: Food and Drug Administration. 11 June 2009. Retrieved 20 July 2014. '''Schedule I drugs''' are (these are all requirements): ::: The drug or other substance has a high potential for abuse. ::: The drug or other substance has no currently accepted medical use in treatment in the United States. ::: There is a lack of accepted safety for use of the drug or other substance under medical supervision. Examples include: diamorphine, cannabis, lysergide and numerous other drugs. '''Schedule II drugs''' are: ::: The drug or other substance has a high potential for abuse. ::: The drug or other substance has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions. ::: Abuse of the drug or other substances may lead to severe psychological or physical dependence. Examples include: nabilone, draonabinol, nabiximols, morphine and cocaine. '''Schedule III drugs''' are: ::: The drug or other substance has a potential for abuse less than the drugs or other substances in schedules I and II. ::: The drug or other substance has a currently accepted medical use in treatment in the United States. ::: Abuse of the drug or other substance may lead to moderate or low physical dependence or high psychological dependence. '''Schedule IV drugs''' are: ::: The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule III. ::: The drug or other substance has a currently accepted medical use in treatment in the United States. ::: Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule III. '''Schedule V drugs''' are: ::: The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule IV. ::: The drug or other substance has a currently accepted medical use in treatment in the United States. ::: Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule IV. Disease/drug terms Nervous system '''Anxiolytic''' – anxiety relieving. '''Dysphoria''' – basically the opposite of euphoria, an unpleasant mood often involving anxiety and/or depression. '''Psychosis''' – a state of experiencing hallucinations and delusions. '''Mania''' – a dangerously happy/high mood. '''Hypomania''' – a less severe form of mania. '''Grandiosity''' – having an excessively high opinion of oneself. Cognition – one’s ability to think, remember, learn, concentrate, problem-solve, ''etc.'' '''Status epilepticus''', a prolonged (over 30 minutes long) and life-threatening seizure. Either that or several smaller seizures that occur in quick succession for a prolonged period of time. '''Anxiolytic''' (two parts of the word – anxio, referring to anxiety, and lytic meaning to destroy) – an anti-anxiety medicine. '''Anxiogenic''' – anxiety-provoking. '''Depressogenic''' – depression-inducing. '''Tardive dyskinesias''', a persistent (often considered irreversible) movement disorder caused by antipsychotic medicines, even after they are withdrawn (i.e., stopped). Analgesia, pain relief. '''Analgesic''', painkiller. '''Neuropathic''', nerve injury-related, for example, neuropathic pain is pain that is related to nerve injury. Sedation, drug-induced sleep. '''Cerebral''', refers to the cerebral cortex, which is the outermost part of the brain and is where all information processing and thought occurs. '''Amnesia''' refers to memory loss. '''Cerebrovascular accident''' – stroke, that is, a blockage of blood supply to the brain. '''Ischaemic stroke''', a blood clot to the brain, leading to oxygen deprivation to the tissues of the brain, leading to irreversible brain damage. '''Haemorrhagic stroke''', a dangerous bleed in the brain. '''Neurodegeneration''' – a (often due to a disease process) process in which neurons die. Diseases that involve neurodegeneration are called '''neurodegenerative disorders''' (NDs). '''Parkinson’s disease''' (PD) – a rare neurodegenerative disorder that leads to the gradual destruction of the dopamine-signalling (“dopaminergic”) neurons of the substantia nigra, which is required for voluntary muscle control. Treatment can significantly improve life expectancy, quality of life, ''etc.'' Treatment usually consists of '''dopaminergic drugs''' such as levodopa, monoamine oxidase B inhibitors, dopamine agonists, ''etc.'', but is not, by any means, curative. Death usually occurs from complications of immobility (i.e., the inability to move) like pneumonia and pulmonary embolism (blood clot to the lung, usually the result of a deep vein thrombosis, a blood clot that forms, predominantly, in the calf muscle of the upper thigh, due to immobility [particularly common during long aircraft flights], that slips loose and goes to the lungs). It is the second most common ND, after '''Alzheimer’s disease'''. '''Alzheimer’s disease''' (AD) – a neurodegenerative disorder that most commonly occurs in the elderly (although some people get it as early as age 30) and causes the progressive loss of cognitive function. Many people think that AD is a normal part of ageing, see while ageing does generally cause slow declines in cognitive function AD produces significantly faster reductions in cognitive skills. It is inevitably fatal, also most commonly due to complications of immobility. Heart '''Myocardial infarction''' – heart attack, that is, a blood clot to the heart. '''Haemorrhage''' – bleeding. '''Cardiomyopathy''' – long-term heart muscle disease, which can progress to heart failure, potentially requiring a transplant. '''Oedema''' (or edema in the U.S.) – the collection of fluid in an area of the body, leading to swelling. '''Hypertension''', high blood pressure. '''Hypotension''', low blood pressure. '''Arrhythmia''', irregular heart rate. '''Tachycardia''', high heart rate. '''Bradycardia''', low heart rate. '''Hypertensive heart disease''', a heart condition that is caused by chronic, uncontrolled hypertension, leading to changes in the heart’s structure and function. Blood '''Coagulopathy''', pathological changes in blood clotting. '''Hyponatraemia''' means low blood sodium, which can, if left uncorrected, can lead to cerebral oedema, seizures and coma. '''Vasoconstriction''', the constriction (i.e., contraction or reducing in diameter) of blood vessels (either arteries or veins). '''Agranulocytosis''', a condition in which the number of immune cells in the blood is dangerously low, so low, in fact, that people experience potentially fatal infections. '''Thrombosis''', a blood-clot. Lung '''Emphysema''', a relatively rare and inevitably fatal condition that causes the lungs to gradually waste away, in essence, leading to breathing difficulties and, eventually death. It is also referred to as '''chronic obstructive pulmonary disease''' (COPD). It nearly always occurs as a result of exposure to either asbestos or tobacco smoke. '''Emesis''' – vomiting. '''Antiemetic''', a nausea and/or vomiting relieving or preventing medicine. Digestive tract '''Emetic''', nausea/vomiting-inducing. '''Gastroprokinetic''', basically refers to drugs that increase the movement of food through the digestive tract. '''Postoperative nausea and vomiting''', nausea and vomiting that occurs after surgery, often related to anaesthesia or the analgesics patients require after the surgery. '''Cirrhosis''', irreversible liver damage. Genitourinary tract '''Erectile dysfunction''', impotence, the inability of a guy to achieve and maintain an erection, despite sexual stimulation. '''Urinary retention''', the inability to pass urine, which is actually pretty dangerous considering the fact that the body uses urine as a way of disposing of toxins. '''Priapism''', a sustained (like over 3 hours) and/or painful erection. '''Rhabdomyolysis''' – the catabolism of muscle leading to the accumulation of myoglobin in the tissues of the body leading, potentially, to kidney failure. '''Diuresis''' increased urine production. Drug reactions '''Serotonin syndrome''', is a constellation of symptoms associated with excess serotonin in the CNS, including: diarrhoea, high heart rate, hypertension, mental status changes (including mania, confusion and psychosis), seizures, coma, high body temperature, ''etc.'' A related condition is called '''neuroleptic malignant syndrome''', which produces many of the same symptoms but they come on more slowly, are due to impaired dopamine activity in the nervous system. It results from exposure to anti-dopaminergic agents. '''Hypertensive crises''', a state characterised by dangerously, in the short-term, high blood pressure so high that it can cause a stroke, heart attack or organ failure. Miscellaneous others '''Lethal Median Dose''' (LD50) – the individual dose of a drug (i.e., for an individual person/animal), or chemical, that is sufficient to kill half of a population of said organism. It is often given as a dose per kilogram of body weight, as the heavier you are the higher the dose of a poison/drug that is required to kill you. The LD50 varies according to the route by which a drug/poison is given, e.g. if it is given orally, intravenously or inhalation. For example, the LD50 of botulinum toxin is 1.3-2.1 ng/kg (ng=nanogram) when administered intravenously. '''Effective Median Dose''' (ED50) – the minimum amount of a drug that is required to produce a therapeutic effect. '''Therapeutic index''': the ratio of LD50 and ED50 (i.e., \frac{LD_{50}}{ED_{50}} ). This ratio gives one an idea of how easy it is to accidentally OD on a drug. '''Oral''', per os, PO, by mouth. '''Diaphoresis''' – excessive/inappropriate sweating (i.e., sweating due to reasons other than temperature). '''Mydriasis''' – dilated pupils. '''Symptomatic''' – basically means pertaining to the symptoms of a disease, e.g. some diseases can only be treated symptomatically, these treatments relieve the symptoms of the condition in question but do not seem to affect the progression of said disease. '''Hyperthermia''', high body temperature. '''Aetiology''' (or etiology in the U.S.) is a fancy way of saying the cause of something. For example, the neurotransmitter glutamate is implicated in the aetiology of the psychiatric disorders schizophrenia and major depressive disorder. '''Knockout mice''', basically mice born without a particular protein, whether it be a receptor, or not. '''Mortality''', death. The '''placebo effect''' is basically that many people just get better because they think they will as their quack has given them a treatment for the condition they trust their doctor telling them that the medicine they are given will make them better. '''Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition''', abbreviated as DSM-5, a publication of the '''American Psychiatric Association''' (APA) that puts forth standards for the accurate diagnosis of psychiatric disorders. '''International Classification of Diseases, Tenth Edition''', abbreviated as ICD-10 is a publication of the '''World Health Organization''' that puts forth standards for the diagnosis of diseases, both physical and mental. '''World Health Organization’s List of Essential Medicines''' (WHO-EM) are a list of medicines that are believed to be the bare minimum necessary for a basic healthcare system. The latest edition of this list may be found here. This is sometimes quoted in-text, in which case I provide page numbers in the following citation format: (WHO-EM, pp. #). Types of clinical trials There are three major types of clinical trials: '''placebo-controlled''', '''open-label''' and '''observational clinical trials'''. '''Placebo-controlled trials''' are considered the gold-standard and highest quality of the three types of clinical trials. They are basically where patients are given either a placebo or the real drug. These trials are the gold-standard as they tell us whether or not any benefits purportedly caused by the drug was due to the drug or due to a placebo effect. However, I should note, that most placebo-controlled trials are also '''randomized''' and '''double-blind''' and these are really the ones that are considered the gold-standard studies (the abbreviation I will assign these trials is RDBRCTs). Randomization means that patients are randomly assigned either the placebo or the real drug. Double-blind means neither the quack that gives the person the drug nor the patient knows whether or not they are getting the real drug or not. The major problem with these trials is that sometimes the drug they are assigned produces such prominent, noticeable or otherwise obvious side effects like drowsiness that it is difficult to know for certain that the patients have been truly fooled into thinking they could have been randomized to receive a placebo. '''Open-label studies''' are basically what they sound like, the patient is given the drug and know what they are getting, there are no patients given a placebo. Open-label studies are considered the lowest-quality. '''Observational studies''', also known as '''cohort studies''', are basically what they sound like, there is no process of randomization involved, no one is assigned a placebo, but rather what we do is we look at what happens to those given the drugs and compare their outcomes to (hopefully) well-matched members of the general population that are not taking the drug. Observational studies are tricky to assign a strength to their generalized quality, except to say they are inferior to the gold standard RDBRCTs, but usually superior to open-label studies. The major reason why is that their quality really does depend on how well they were matched to those not taking the drug. Types of secondary evidence '''Reviews''' are '''journal articles''' written by experts in their fields, usually doctors, researchers or pharmacists, in order to review currently available information in a way that is accessible to the reader. They usually include published and unpublished data from clinical trials, especially RDBPCTs. '''Systematic reviews''' are more methodical reviews and often mathematically analyse the available data. '''Meta-analysis''' is a statistical analysis of clinical trial data, especially data from RDBPCTs. Published textbooks are also considered high quality medical information. Review articles and published textbooks are generally considered the '''highest quality medical information''' there is. Reference list